Of mitogens and morphogens: modelling Sonic Hedgehog mechanisms in vertebrate development

Abstract

Sonic Hedgehog (Shh) Is a critical protein in vertebrate development, orchestrating patterning and growth in many developing systems. First described as a classic morphogen that patterns tissues through a spatial concentration gradient, subsequent studies have revealed a more complex mechanism, in which Shh can also regulate proliferation and differentiation. While the mechanism of action of Shh as a morphogen is well understood, it remains less clear how Shh might integrate patterning, proliferation and differentiation in a given tissue, to ultimately direct its morphogenesis. In tandem with experimental studies, mathematical modelling can help gain mechanistic insights into these processes and bridge the gap between Shh-regulated patterning and growth, by integrating these processes into a common theoretical framework. Here, we briefly review the roles of Shh in vertebrate development, focusing on its functions as a morphogen, mitogen and regulator of differentiation. We then discuss the contributions that modelling has made to our understanding of the action of Shh and highlight current challenges in using mathematical models in a quantitative and predictive way. This article is part of a discussion meeting issue 'Contemporary morphogenesis'.